Inhibition of Cdk5 in PV Neurons Reactivates Experience-Dependent Plasticity in Adult Visual Cortex

• Published in: International journal of molecular sciences 2021-12, Vol.23 (1), p.186
• Main Authors: Zhang, Xinxin, Tang, Huiping, Li, Sitong, Liu, Yueqin, Wu, Wei, Li, Yue, Ma, Chenchen, Ma, Xiao, Chen, Lin, Yang, Yupeng
• Format: Article
• Language: English
• Subjects: Ablation; Action potential; Alzheimer's disease; Animals; Cdk5; Central nervous system; Cocaine; Cyclin-dependent kinase 5; Cyclin-Dependent Kinase 5 - genetics; Cyclin-Dependent Kinase 5 - metabolism; Cyclin-Dependent Kinase 5 - physiology; Cyclin-dependent kinases; Dominance, Ocular; Firing rate; Gene Knockdown Techniques; Hyperpolarization; Information processing; Interneurons; Kinases; Male; Membrane potential; Mice; monocular deprivation; Neuroimaging; Neuronal Plasticity; Neurons; Neurons - metabolism; Neurons - physiology; Neuroplasticity; Ocular dominance; ocular dominance plasticity; Optical communication; Parvalbumin; primary visual cortex; PV neurons; Rodents; Threshold currents; Visual cortex; Visual Cortex - enzymology; Visual Cortex - physiology; Visual plasticity; Visual signals
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010186

Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.